Process of making dialkyl barbituric acid.



. isobtained.

such as sodium nitrite, is added to the acetic i UNITED STATES Patented January 17, 1905.

PATENT OFFICE.

KARL STEPHAN AND PAUL HUNSALZ, OF BERLIN, GERMANY, ASSIGNORS TO OHEMISGHE FABRIK'AUF ACTIEN, (VORM. E. SCHERING,) or BER- -LIN, GERMANY.

DIALKYL BARBITURIC ACID.

SPECIFICATION forming part of Letters Patent No. 780,241, dated January 17, 1905.

Application filed September 27,1904. Serial No. 226,18.

To all whom it may concern:

Be it known that we, KARL STEPHAN and PAUL HUNSALZ, subjects of the German Em- 'p'ei'or, residing at Berlin, Kingdom of Prussia, German Empire, have invented a new and useful Improvement in Processes of Manufacituring Dialkyl Barbituric Acids, of which the following is a specification.

. According to our invention dialkyl barbituric acids, which are known as valuable soporifics andwhich have the general formula,

are manufactured by oxidizing in acid solution the corresponding dialkyl-malonyl-guani dins, answering the general formula:

These guanidin derivatives do not possess any fixed melting-point and are insoluble in water and chloroform. A good yield of the req'uired dialkyl barbituric acids is quite easily obtained in this manner.

By the action of the oxidizing agent in acid solution the im'ido group (NH) is not merely split of! by the acid, but oxidization really takes place. Thus, for example, by the action of nitric oxid upon guanin xanthin is produced, whereas xanthin is not formed when guanin is acted upon by acids. It is similar in the following cases. If, for exam ple, acetic acid is allowed to react upon diethyl-malonylguanidin, no trace of diethyl barbiturie acid If, however, an oxidizing agent,

acid. complete con ersion ensues. If mineral aclds be employed, the conversion takes place more quickly in thepresence of an oxidizing agent'tha'n with no oxidizing agent.

stance, be obtained in the following ways:-

First. One kilogram of dicthyl-malonylguanidin (which is made either by allowing guanidin rhodanate and sodium alcoholate to react upon diethyl-malonie acid ester or by starting-from in'onoethyl-malonic acid ester, condensing it with guanidin rhodanate and sodium alcoholate'and then inserting the second ethyl group) is dissolved in seventeen grams of dilute sulfuric acid, (twelve per eent.,) and when the mixture is at 100 centigrade a concentrated aqueous solution of so dium nitrite is added to it while stirring well. After cooling the mixture is -made exactly neutral with ammonia. By concentrating the liquid the diethyl barbituric acid; which is with difliculty soluble in water, separates out. By recrystallizing from water the product is further purified.

Second. One kilogram of diethyl-malonylguanidin' is suspended in ten kilograms of of chromic acid is slowly added to the warmed mixture. The mixture is then heated for a cooling thediethyl barbituric acid is extracted from the liquid by shaking with chloroform.

Third. One kilogram of diethyl-rnalonylguanidin is suspended in ten kilograms of twenty per cent. acetic acid, and to this mixture one kilogram of sodium nitrite in soluprocess proceeds as above. 7 Fourth. One kilogram of guanidin has added to it a solution of one kilo gram of chromic acid in thirty liters of water. After lengthened heating solution takes place. After cooling the diethyl barbiturlc acid formed is extracted by shaking with a solvent.

The production of other alkyl derivatives is carried out in an analogous manner by starting with the corresponding alkyl-malonylf guanidin, I l The dimethyl barbituric stance, produced as follows: dimethyl-malonyl-guanidin,

acid is, for in- One kilogram of which is form The dialkyl barbituric acids may, for inshort time until solution takes place, and after.

twenty percent. acetic acid,and one kilogram tion is slowly added.' The remainder of the diethyhmalonyl- Correction in Letters Patht No. 780,241.

in an analogous manner to the tliethyl cornkyl barbituric acids thus formed, substautiallx pound, is dissolved in seventeen kilograms of as described. 1 twelve-per-cent. sulfuric acid, and at 100 2. Process of producing cliet-hyl barbituric ccntigradeaconcentratodaqueous solutionof acid, which consists in oxidizing diethyl- 5 sodium nitrate is added while stirring We'll. malonyl-guanidin in acid solution and scpa After cooling the mixture is made neutral rating-thediethyl barbituricacid thus for-med, with ammonia. By concentrating the liquid substantially as described, a

the cliniethyl barbituric acid, which is difii- In testimony whereof we have hereunto set cultly soluble in cold water, separates out. our names in the presence of two subscribing 5 I0 It has alinelting point of 265" centigrade. witnesses.

'ec aim as our invention-- v Q, i v 1. Process of producing dialkyl bai'bituric acids, having-the hereinbefore-mentioned genv i eral formula, which consists in oxidizing the Vitnesses: 5 corresponding" dialkyl-malonyl-guanidins in I'IENRY HASI'ICR,

the presence of acids and separating the dial- \VoLDmL-m liAUlT.

It is hereby certified that in Letters Patent No. 780,241 'rauted January 17,1995, upon the application of Karl Stephan and Paul Hunsalz, of' Berlin, Germany, for an improvement in Processes of making Dialky] Barbituric Acid, an error appears in j the printed pecificatiou requiring correction, as follows: In line 5, page 2, the word nitrate" should read nitrite; and that the said Letters Patent should be read with this correction Lliuruin that the same may conform to the record of the case in the Patent ()flivv.

Signed and scaled this 14th day of February, A. 1)., 1905. I

[SEAL.] F. I. ALLEN,

C'omm'issivne-r of Patents.

Correction in Letters Patht No. 780,241.

in an analogous manner to the tliethyl cornkyl barbituric acids thus formed, substautiallx pound, is dissolved in seventeen kilograms of as described. 1 twelve-per-cent. sulfuric acid, and at 100 2. Process of producing cliet-hyl barbituric ccntigradeaconcentratodaqueous solutionof acid, which consists in oxidizing diethyl- 5 sodium nitrate is added while stirring We'll. malonyl-guanidin in acid solution and scpa After cooling the mixture is made neutral rating-thediethyl barbituricacid thus for-med, with ammonia. By concentrating the liquid substantially as described, a

the cliniethyl barbituric acid, which is difii- In testimony whereof we have hereunto set cultly soluble in cold water, separates out. our names in the presence of two subscribing 5 I0 It has alinelting point of 265" centigrade. witnesses.

'ec aim as our invention-- v Q, i v 1. Process of producing dialkyl bai'bituric acids, having-the hereinbefore-mentioned genv i eral formula, which consists in oxidizing the Vitnesses: 5 corresponding" dialkyl-malonyl-guanidins in I'IENRY HASI'ICR,

the presence of acids and separating the dial- \VoLDmL-m liAUlT.

It is hereby certified that in Letters Patent No. 780,241 'rauted January 17,1995, upon the application of Karl Stephan and Paul Hunsalz, of' Berlin, Germany, for an improvement in Processes of making Dialky] Barbituric Acid, an error appears in j the printed pecificatiou requiring correction, as follows: In line 5, page 2, the word nitrate" should read nitrite; and that the said Letters Patent should be read with this correction Lliuruin that the same may conform to the record of the case in the Patent ()flivv.

Signed and scaled this 14th day of February, A. 1)., 1905. I

[SEAL.] F. I. ALLEN,

C'omm'issivne-r of Patents.

It is hereby certified that in Letters Patvnt No. 780,241 grauted January I7, 1995,

upon the application of Karl Stephan and Paul Hunsalz, of Berlin, Germany, fdr an improvement; in "Processes of making Dialkyl Barbitnric Acid, an error appears in Correction in Letters Patent No. 780,241.

the printul .-pc( :ilic:\tinn requiring correction, as follows: In line 5, page 2, the word nitrate" shnuhl rt-ml icilritc; and that the said Letters Patent should be read with this correction Lln-rvin that the same may conform to the record of the case in the Patent ()tlir-v.

Signed and sonh-(l this 14th day of February, A. IJQ 1210-3.

[SEAL] F. I. ALLEN,

Fommissiuner of Patents. 

